Our mission is to improve the treatment, quality of life and the long term outlook for children and adults living with hyper igm through research, support, education, and advocacy to. The igm is not usually as high as is seen in classic hyper igm syndrome. Jun 25, 20 the hyper igm syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the cd40 ligandcd40 signaling pathway. Hyperigm syndrome type 5 characterized by mutations of the ung gene. May 31, 2007 xlinked hyper igm syndrome higm1, a disorder of abnormal t and bcell function, is characterized by low serum concentrations of igg, iga, and ige with normal or elevated serum concentrations of igm. However, because these symptoms, such as a high fever, are typical in early childhood, many doctors and parents may not recognize the symptoms as being abnormal until the child is older. Hyper igm syndrome is a primary immunodeficiency disorder in which the childs body fails to produce certain specific types of antibodies. Idf 2017 national conference session, hyper igm syndrome higm was presented by caroline kou, md on june 16, 2017. Hyperigm syndrome type 3 is a form of hyper igm syndrome characterized by mutations of the cd40 gene. It causes immunodeficiency and susceptibility to infections. In this type, immature b cells cannot receive signal 2 from helper t cells which is necessary to mature into mature b cells. Hyper igm syndrome type 5 characterized by mutations of the ung gene. Hyper igm syndrome immunologic phenotype presenting with low igg, iga, and ige levels with normal or increased igm levels the term hyperigm is a misnomer igm levels are not necessarily high the relative excess of igm is due to a defect in class switch recombination csr in certain cases somatic hypermutation shm is also affected uygungil.
The clinical course of xlinked hyper igm syndrome is similar to that of xlinked brutontype agammaglobulinemia except for a greater frequency of autoimmune hematologic disorders neutropenia, hemolytic anemia, thrombocytopenia. It is the most common form of hyperigm syndrome, accounting for approximately 70% of cases. Causes of hyperigm syndrome including triggers, hidden medical causes of hyperigm syndrome, risk factors, and what causes hyperigm syndrome. The other forms of hyper igm syndrome have only been described in the medical literature in a very small number of people. Despite the name, high levels of igm are inconsistently found in all forms of hyperigm syndrome. Hyperigd syndrome pediatrics merck manuals professional. Hyper igm syndrome an overview sciencedirect topics. Mevalonate kinase deficiency nord national organization. Hyper igm syndromes are a group of rare disorders in which the immune system. See also overview of immunodeficiency disorders and approach to the. Mutation of the cd40l gene in xlinked hyperigm syndrome.
Autosomal dominant hyperige syndrome genetics home. Because isotype switching of antibody cannot occur, there is a selective hypogammaglobulinemia of igg, iga, and ige. Doctors and medical specialists for hyperigm syndrome. Mendelian inheritance of immunodeficiency disorders.
Hyper igd syndrome is the less severe form of a metabolic disorder known as. Hyper igm syndrome is caused by genetic mutations of genes involved in immune response and affects a very small part of population. Hyperigm syndrome immune disorders msd manual consumer. Hyperigm syndrome higm is a descriptive term that reflects a common laboratory abnormality high serum igm level with low serum iga and igg levels found in several otherwise dissimilar types of immunodeficiencies table 925. An update on the hyperige syndromes arthritis research. The term hyper igm syndrome identifies a heterogeneous group of genetically inherited disorders that are characterized by susceptibility to opportunistic infections and decreased serum levels of igg and iga, but normal or elevated igm. Lurie childrens hospital of chicago, northwestern university feinberg school of medicine, chicago, il, usa. Recurrent infections are common in people with this condition. The bodies of people with primary immunodeficiency cant get rid of germs or protect themselves from new germs as well as they should. The term primary means that the disorder is present from birth, in contrast to secondary immunodeficiencies such as aids, which are acquired later in life by previously healthy persons. The diagnosis of hyper igm syndrome can be done via the following methods and tests. Hyper igm syndrome patients with the hyper igm syndrome have an inability to switch their antibody immunoglobulin production from igm to igg, iga, and ige. The lesions had increased in number and in size but had not caused any problems with pain, movement, or playing. One would expect opportunistic infections in any immunodeficiency syndrome.
The hyper igm syndrome higm is one of the rarest primary immunodeficiencies. To research the causes of hyperigm syndrome, consider researching the causes of these these diseases. This kind of hyper ige syndrome is acquired by autosomal dominant inheritance whereby if one of the parents is affected, then chances of passing the abnormal gene to the child is about 50%. What are the clinical characteristics of hyper ige syndrome. Hyper igm syndrome is a collective name for a heterogeneous group of disorders united by defects in antibody isotype class switching and somatic hypermutation.
They can be classified as defects of signalling through cd40 causing both a. The most common and the most clinically severe of these is an xlinked deficiency in cd40 ligand cd40 l. Mutations of cd40, the receptor for cd40l, cause a rare autosomal form of. For the other 3 mutations, they run in an autosomal recessive manner, this is, the chances to have the condition is 25%, increasing if the parents are. However, it is important to note that patients may also have normal levels of all immunoglobulins early in life. Mar 10, 20 hyper igm syndrome immunologic phenotype presenting with low igg, iga, and ige levels with normal or increased igm levels the term hyper igm is a misnomer igm levels are not necessarily high the relative excess of igm is due to a defect in class switch recombination csr in certain cases somatic hypermutation shm is also affected uygungil. The nemo deficiency syndrome is a complex disease caused by genetic mutations in the xlinked nemo gene also known as ikk gamma or ikkg. As a result, people are more susceptible to bacterial infections. Hyper igm syndrome type 1 higm1 is the xlinked variant of the hyper igm syndrome. The characteristic facial features are usually set by age 16. Hyper igm syndromes is a group of primary immune deficiency disorders characterized by.
The most common form of hyper igm is xlinked hyper igm, which primarily affects boys, except in rare cases. Xlinked hyper igm syndrome genetics home reference nih. There are at least four types of autosomal recessive hyper igm syndrome. Autosomal dominant hyperige syndrome caused by stat3 defects, called job syndrome, have characteristic facial, dental, and skeletal abnormalities.
Hyper igm syndrome type 2 is estimated to affect fewer than 1 in 1,000,000 people in the general population. The autosomal recessive forms of hyper igm syndrome are extremely rare. Diagnosis of hyper igm syndrome is suspected based on clinical criteria, including recurrent sinopulmonary infections, chronic diarrhea, and lymphoid hyperplasia. Our mission is to improve the treatment, quality of life and the long term outlook for children and adults living with hyper igm through research, support, education, and advocacy to families and patients. Since the autosomal recessive forms of higm require that the gene on both chromosomes be affected they are less common than the xlinked conditions. The hyper igm syndromean evolving story pediatric research. Hyper igm syndrome can be caused by at least four different molecular genetic defects, 16 the most common of which affects the gene on the x chromosome encoding cd40 ligand, a tcell surface molecule responsible for instructing b cells to switch from igm to igg, iga, and ige production. Autosomal dominant hies has been shown to be mainly due to stat3 mutations. Hyper igm syndrome is a very rare disease that affects only 1 in 1,000,000 individuals. Hyper ige syndrome is an immune deficiency caused by a genetic mutation in either stat3 autosomal dominant, also known as jobs syndrome or dock8 autosomal recessive there may be other mutations in other genes that are not known at this time. Hyperigm syndrome definition hyperigm syndrome is a primary immunodeficiency disorder in which the childs body fails to produce certain specific types of antibodies. A novel homozygous mutation in recombination activating gene 2 in.
Hyperigm syndrome a case report and a clinical perspective. Children with hyperigm syndrome have frequent sinus and lung infections. For a discussion of genetic heterogeneity of immunodeficiency with. We report a novel mutation of the cd40l gene in xlinked hyperigm syndrome xhigm in two sibling chinese patients, about which we made a literature. Autosomal dominant hyper ige syndrome adhies is a primary immune deficiency characterized by the classic triad of recurrent skin boils, cystforming pneumonias, and extreme elevations of serum ige. Hyperigm syndrome is an immunoglobulin ig deficiency characterized by normal or elevated serum igm levels and decreased levels or absence of other serum immunoglobulins, resulting in susceptibility to bacterial infections. Symptoms of higm syndrome usually appear within the first 2 years of life and may include1,2. Jun 26, 2017 hyper igd syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency. Cd40 ligand is expressed on activated t lymphocytes and is necessary for t cells to induce b cells to undergo immunoglobulin. Xlinked hyper igm syndrome is a condition that affects the immune system and occurs almost exclusively in males. This book contains general medical information and is intended to provide the patient and family with tools to enhance the. The diagnosis of xlinked hyper igm syndrome is established in a male.
The hyper igm syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the cd40 ligandcd40 signaling pathway. In terms of treatment for hyper igm syndrome, there is the use of allogeneic hematopoietic cell transplantation. Immunodeficiency with hyper igm type 1 genetic and rare. Hyper igm syndrome type 4 which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hypermutation. Practice mendelian inheritance of immunodeficiency disorders with khan academys free online exercises. Hyper igd syndrome is a rare autosomal recessive disorder in which recurring attacks of chills and fever begin during the first year of life. Xlinked immunodeficiency with hyperimmunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39. Xlinked hyper igm xhigm and nemo with immunodeficiency are inherited as xlinked recessive disorders, and only boys are affected. Oct 23, 2019 xlinked immunodeficiency with hyper immunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39. It is now recognized that other common manifestations include eczema, mucocutaneous candidiasis, and several connective tissue and skeletal abnormalities.
Primary immunodeficiency occurs when part of a persons immune system is missing or does not work correctly. The most common symptoms are skin disease and susceptibility to certain bacterial infections that can be severe and affect. Proliferation of igm producing plasma cells may lead to. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. It can involve many different parts of the body and often manifests in different ways in different individuals. Hyper igd syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency.
Hyper igm syndromes nord national organization for rare. Proliferation of igmproducing plasma cells may lead to. Hyperigm syndrome is characterized by normal or high levels of immunoglobulin m igm and decreased levels or absence of other immunoglobulins. Diagnosis of hyperigm syndrome is suspected based on clinical criteria, including recurrent sinopulmonary infections, chronic diarrhea, and lymphoid hyperplasia. Symptoms are usually present before the age of one. It is considered an autoinflammatory disease, with recurrent episodic or chronic unexplained inflammation, characterized by periodic episodes of fever, and other symptoms such as joint pain, swollen lymph nodes, skin rash, headaches, and abdominal pain. Hyper igm syndrome is an immunoglobulin ig deficiency characterized by normal or elevated serum igm levels and decreased levels or absence of other serum immunoglobulins, resulting in susceptibility to bacterial infections. Hyper igm syndrome is an immunodeficiency disease that results from an. They differ by the nature of underlying genetic defect. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction.
Since the autosomal recessive forms of higm require that the gene on both chromosomes be affected, they are less frequent than the xlinked conditions. Hyperigd syndrome is a rare autosomal recessive disorder in which recurring attacks of chills and fever begin during the first year of life. A number of different genetic defects can cause the hyper igm syndrome. Mitogen proliferation may be normal, but nk and tcell cytotoxicity can be impaired. Xlinked hyper igm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. As a result, patients have decreased levels of igg and iga and normal or elevated levels of igm. The hyperimmunoglobulin m syndromes higm are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination csr, with or without defects of somatic hypermutation shm. Hyperigm syndrome definition of hyperigm syndrome by.
Hyper igm syndrome is a type of primary immunodeficiency syndrome. Recently, one lesion on the left knee had become slightly red. Antigenspecific responses are usually decreased or absent. Nemo deficiency syndrome immune deficiency foundation. Episodes usually last 4 to 6 days and may be triggered by physiologic stress, such as vaccination or minor trauma. What is xlinked hyperigm syndrome xlinked hyperigm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. Xlinked hyper igm syndrome higm1, a disorder of abnormal t and bcell function, is characterized by low serum concentrations of igg, iga, and ige with normal or elevated serum concentrations of igm. Affected individuals can fall anywhere along this spectrum and it is important to remember every person is unique and the disorder may affect them differently from how it affects another person. This variant of the hyper igm syndrome is caused by mutation of the cd40lg gene.
Patients with stat3 hies may have either delay of or failure in shedding of primary teeth. Aug 30, 2017 idf 2017 national conference session, hyper igm syndrome higm was presented by caroline kou, md on june 16, 2017. Hyper igm syndrome type 2 higm2 is a rare immunodeficiency characterized by normal or elevated serum igm levels with absence of igg, iga, and ige, resulting in a profound susceptibility to bacterial infections. Due to the progress in understanding of this condition, achieved in the recent. The disorder has autosomal dominant and recessive forms. Hyper igm syndrome, which is characterized by the presence of normal or elevated serum levels of igm and low igg and iga, may be caused by one of at least 10 gene defects table 17. Xlinked hyper igm xhigm and nemo with immunodeficiency are inherited as xlinked recessive disorders and only boys are affected. Aug 01, 20 a collection of disease information resources and questions answered by our genetic and rare diseases information specialists for immunodeficiency with hyper igm type 1. For a discussion of genetic heterogeneity of immunodeficiency with hyper igm, see higm1 308230. It is the most common form of hyper igm syndrome, accounting for approximately 70% of cases. N2 the hyper igm syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the cd40 ligandcd40 signaling pathway. Unlike other hyper igm syndromes, the type 2 patients identified thus far did not present with a history of opportunistic infections. The hyper igm syndromes are a group of rare inherited immune deficiency disorders. Patients with nemo syndrome may have an elevated igm or iga, but not both.
Hyperigm syndrome is a collective name for a heterogeneous group of disorders united by defects in antibody isotype class switching and somatic hypermutation. In addition to the susceptibility to pyogenic infections, male patients are prone to pneumocystis carinii infections and autoimmune diseases, mainly directed against blood cells hemolytic anemia, thrombocytopenia, and neutropenia. B essential modulator, while autosomal recessive forms of hyper igm are caused by defects in cd40 or. Hyperigm syndrome type 2 higm2 is a rare immunodeficiency characterized by normal or elevated serum igm levels with absence of igg, iga, and ige, resulting in a profound susceptibility to bacterial infections. Xlinked forms of hyper igm are caused by defects in the cd40 ligand gene or nf. The putative genetic lesion is in the aicda gene found at 12p. B essential modulator, while autosomal recessive forms of hyper igm are caused by. Neutropenia responds to ivig and granulocyte colonystimulating factor gcsf.
The hyperigm syndrome higm is one of the rarest primary immunodeficiencies. Autosomal dominant hyperige recurrent infection syndrome1 hies1. Patient presentation an 18monthold female came to clinic with a history of bumps on her legs for 5 weeks. Some patients with higm have now been identified with a novel form of higm that. The hyper igm syndromes higm are a group of primary immune. Hyperigm higm syndrome is a group of rare, inherited disorders that affect the bodys natural defense immune system. Winkelstein, in comprehensive pediatric hospital medicine, 2007. Hyperige recurrent infection syndrome 2, autosomal. Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. Hyperigm syndrome type 4 which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hypermutation. Hyperigd syndrome genetic and rare diseases information. Autosomal dominant hyperige syndrome adhies, formerly known as job syndrome, is a condition that affects several body systems, particularly the immune system. Manis jp, alt fw 2003 novel antibody switching defects in human patients.
1450 866 193 735 1385 345 659 522 1216 69 21 151 863 218 311 1246 318 1366 40 655 561 849 441 985 1131 174 499 165 936 830 1417 670 575 175 345 154 1275 414 1456